Thermosensitive Injectable Hydrogel Incorporating Telopeptide-Free Type I Collagen Promotes Cartilage Regeneration: An In Vivo Study.

Abstract

Background: In cartilage tissue engineering, successfully mimicking the natural extracellular matrix is essential for promoting hyaline cartilage regeneration. The triple-helix structure of collagen has been identified as a critical element in this process, though preserving this structure while minimizing immunogenicity remains a significant challenge.

Methods: This study employed high-precision enzymatic digestion technology to specifically remove immunogenic terminal fragments from collagen while preserving its functional triple-helix configuration. The resulting collagen-based hydrogel was engineered with thermosensitive properties, enabling it to adaptively fill irregular cartilage defects and undergo rapid gelation at body temperature.

Result: The modified collagen hydrogel demonstrated significantly improved biological safety, with complement activation levels substantially decreasing following removal of terminal peptide segments-confirming the immunogenic role of these regions. Mechanically, the hydrogel successfully replicated the viscoelastic characteristics of natural cartilage, exhibiting matched dynamic mechanical properties capable of cushioning shear-induced damage. Its porous architecture facilitated accelerated nutrient transport while supporting effective cell adhesion and guiding organized proteoglycan deposition with minimal fibrosis. In vivo evaluation revealed a 30.7% higher MOCART score in the experimental group compared to controls, with mechanical properties closely approximating those of healthy native cartilage.

Conclusion: Collagen hydrogels that maintain the triple-helix structure represent a highly promising biomaterial platform for cartilage regeneration, combining excellent biocompatibility, functional mechanical properties, and significant tissue repair capability while effectively addressing the critical challenge of immunogenicity through targeted terminal peptide removal.